Through the integration of a mentored research experience with formal coursework at the Harvard School of Public Health, this proposal will support and enrich the development of Akila N. Viswanathan, MD, MPH, as an investigator committed to an academic career in cancer control and epidemiology. The proposed research will analyze risk factors for endometrial cancer using the Nurses'Health Study database. The analyses will focus on understanding the role of inflammation in the development of endometrial cancer. In Aim 1, the proposed research project will clarify the role of anti-inflammatory medications, including aspirin and non-steroidal anti-inflammatory drugs, in relation to the risk of endometrial cancer and contrast these results to those of acetaminophen, which is not an anti-inflammatory medication. The role of genetic polymorphisms of the enzymes CYP2C9 and UGT1A6 in the metabolism of aspirin in relation to its effect will be studied. Since the role of treatment with anti-inflammatory drugs has not been analyzed in any prior epidemiologic study, this research will provide a more thorough understanding of the underlying etiology and biology of this cancer and provide public health information on the impact of consumption of these agents with regard to dose and duration of use. In Aim 2, we will examine the role of increased inflammation on the risk of endometrial cancer. Specifically, this project will analyze the role of the pro-inflammatory intra-uterine device (IUD) using the Nurses'Health Study prospective cohorts. The role of markers of systemic inflammation will be assessed by a nested case-control analysis of the biomarkers C-reactive protein and interleukin-6, providing the first analysis of these biomarkers in relation to endometrial cancer risk. All analyses will be performed by Dr. Viswanathan. She will acquire experience in analyzing prospective cohort and case-control studies, questionnaires, biomarkers, and genetic polymorphisms. The results of this proposed research will provide important new information about the etiology of endometrial cancer and assist with the assessment of future population risk. Through this grant, Dr. Viswanathan will obtain a doctoral degree in epidemiology, and thereby will have the requisite training to become a true expert in the field. This proposal will ensure that she will become an established independent investigator and a leading expert in gynecologic cancer epidemiology.